A prospective, multicenter, double-randomised, double-blind, 2-parallel groups, phase 3 study to compare as first line therapy efficacy and safety of masitinib in combination with gemcitabine, to gemcitabine in combination with placebo, followed as second line treatment by masitinib in combination with Folfiri.3 versus placebo in combination with Folfiri.3 in the treatment of patients with non resectable locally advanced or metastatic pancreatic cancer.

INTERVENTION: Product Name: masitinib 100mg Product Code: AB1010 Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: masitinib mesylate CAS Number: 790299‐79‐5 Current Sponsor code: AB1010 Other descriptive name: MASITINIB Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 100‐ Pharmaceutical form of the placebo: Film‐coated tablet Route of administration of the placebo: Oral use Product Name: masitinib 200mg Product Code: AB1010 Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: masitinib mesylate CAS Number: 790299‐79‐5 Current Sponsor code: AB1010 Other descriptive name: MASITINIB Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 200‐ Pharmaceutical form of the placebo: Film‐coated tablet Route of administration of the placebo: Oral use CONDITION: Non resectable locally advanced or metastatic pancreatic cancer ; MedDRA version: 18.0 Level: PT Classification code 10033610 Term: Pancreatic carcinoma metastatic System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) Therapeutic area: Diseases [C] ‐ Cancer [C04] PRIMARY OUTCOME: Main Objective: Overall survival (OS) Primary end point(s): • Overall Survival (OS) is defined as the time from the randomization to the date of documented death Secondary Objective: •Survival rate every 24W (weeks); •Tumour assessment: every 8W; ‐Overall Progression Free Survival (PFS) central and local ; ‐PFS rate; ‐Time To Progression (TTP) central and local; ‐TTP rate central and local; ‐Overall TTP (RECIST 1.1); ‐TTP rate (RECIST 1.1); ‐Overall Time to Treatment switch (TTS); ‐TTS rate; ‐Best response along study: Complete response (CR) rate, Partial Response (PR) rate, Progressive disease (PD); ‐Level of serum CA 19‐9 ; •Quality of life assessment: every 4W until W48 then every 8W; ‐EORTC QLQ‐C30 questionnaire ; ‐ECOG Performance Status ; ‐Patient’s visual analogue scale (VAS) and Brief Pain Inventory (BPI) ; ‐Analgesic consumption ; •Pharmacogenomic assessment; Relationship between genomic data and all efficacy variables; •Safety profile (NCI CTC v4.02 classification); ‐Discontinuation for related AE; ‐Related Grade 3 non haematological or any related grade 4 related AE; ‐AE leading to death; ‐Cardiac AE; ‐AE related to cancer pain Timepoint(s) of evaluation of this end point: Date of documented death SECONDARY OUTCOME: Secondary end point(s): Progression Free Survival Timepoint(s) of evaluation of this end point: Every 8 weeks INCLUSION CRITERIA: First randomisation INCLUSION CRITERIA: 1. Histologically or cytologically confirmed adenocarcinoma of the pancreas, non resectable 2. Patient with pain related to the disease, as assessed by the investigator and the patient: ‐ Pain related to the disease as assessed by the investigator is defined as clinical and documented evaluation by the investigator during physical examinations at screening and/or baseline. ‐ Pain, as assessed by the patient is defined as at least one value out of two values > 20mm on Visual Analogic Scale at screening or baseline. Visual Analogic scale consists in the visual representation of pain amplitude as perceived by the patient. The amplitude is represented by a 100 mm long line having no reference marks. One extremity indicates an absence of pain (0 value) and the other the worst imaginable pain (100 value). OR Patient treated with opioid analgesics at a dose = 1 mg/kg/day (morphinic equivalent). OR